Abstract
Insulin resistance and type 2 diabetes are associated with hepatitis C virus infection. A wealth of clinical and experimental data suggests that the virus is directly interfering with the insulin signalling in hepatocytes. In the case of at least one viral genotype (the type 3a), insulin resistance seems to be directly mediated by the downregulation of the peroxisome proliferator-activated receptor γ. Whether and how this interaction may be manipulated pharmacologically, in order to improve the responsiveness to antivirals of insulin resistant chronic hepatitis C, patients remain to be fully explored.
Highlights
Hepatitis C virus (HCV) infection is associated with an increased risk of developing glucose intolerance and diabetes
Since the peroxisome proliferator-activated receptors (PPARs) are nuclear factors involved—among others—in the regulation of glucose homeostasis, the relationship between HCV replication and protein expression and PPARs has been the focus of some recent studies
Most viral genotypes seem to activate members of the suppressors of cytokine signalling (SOCS) family in order to inhibit insulin signalling, in the case of genotype 3a, some in vitro observations are consistent with a downregulation of the PPARγ
Summary
Hepatitis C virus (HCV) infection is associated with an increased risk of developing glucose intolerance and diabetes. Most viral genotypes seem to activate members of the suppressors of cytokine signalling (SOCS) family in order to inhibit insulin signalling, in the case of genotype 3a, some in vitro observations are consistent with a downregulation of the PPARγ If confirmed, these observations may be relevant to the treatment of chronic hepatitis C, since insulin resistance is a factor of poor response to antivirals. PPARα is principally expressed in tissues exhibiting high rates of β-oxidation such as liver, kidney, heart, and muscle, and can be activated by dietary fatty acids and eicosanoids or by specific drugs such as fibrates. Treatment with PPARγ agonists lowers plasma level of free fatty acids and insulin, and increase the phosphorylation level of Akt at both threonine 308 and serine 473 in the liver and both the adipose and muscle tissues [7]. Treatment with PPARs agonists results in improved insulin sensitivity via diverse mechanisms, both direct and indirect, and both at the level of the liver and at the level of extrahepatic tissues
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